Boone has been a professor of art history at Tulane University since 1994–95, holding the Martha and Donald Robertson Chair in Latin American Art. She is also a research associate at Tulane's Middle American Research Institute (MARI).[2] From 2006 Boone took a sabbatical from lecturing and research at Tulane, to accept a position to pursue independent research as the Andrew W. Mellon Professor at the National Gallery of Art's Center for Advanced Study in the Visual Arts (CASVA), an appointment lasting through 2008.[3] Boone had previously been a Paul Mellon Senior Fellow at CASVA, in 1993–94.[2]

After receiving her PhD, Boone secured a research associate position at University of Texas at San Antonio's Research Center for the Arts, where she worked for three years. In 1980 Boone took up a position in pre-Columbian studies at the research institution she would be associated with for the next fifteen years, the Dumbarton Oaks Research Library and Collection located in Washington, D.C.. Initially as associate curator (1980–83) and then as Director of Pre-Columbian Studies and Curator of the Pre-Columbian Collection (1983–95), Boone oversaw and held responsibility for Dumbarton Oaks' research and scholarship programs, symposia and colloquia, scheduled publications and the curatorship of the institution's libraries and collection of pre-Columbian artworks.[2] From 2006 onwards Boone has retained a position as one of the six-member Board of Senior Fellows in pre-Columbian Studies at Dumbarton Oaks.[4]

In 1995 Boone relocated to New Orleans, Louisiana to become professor of art history at Tulane University, where she teaches courses on Mesoamerican, Aztec and colonial-era art history, general art interpretation and theory, and continues to publish research papers and books in the field.